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Analysis of breakpoints within the bcr gene and their correlation with the
clinical course of Philadelphia-positive chronic myelogenous leukemia
M Shtalrid, M Talpaz, R Kurzrock, H Kantarjian, J Trujillo, J Gutterman, G Yoffe and M Blick
Department of Clinical Immunology and Biological Therapy, Hematology,
University of Texas M.D. Anderson Hospital and Tumor Institute, Houston
77030.
Chronic myelogenous leukemia (CML) is characterized by a reciprocal
translocation between chromosomes 9 and 22. The breakpoints on chromosome
22 are clustered within a 5.8-kilobase (kb) DNA fragment known as the
breakpoint cluster region (bcr), which encodes part of a functionally
active gene. We analyzed the bcr in DNAs from 108 consecutive, unselected
Philadelphia chromosome-positive CML patients by Southern blot and
determined five restriction enzyme fragments within which breaks occur on
chromosome 22. The exact sublocalization was determined in the DNA of 100
patients. It was found to be within the 5.8-kb in 99 patients and outside
the bcr in only one. Within the bcr, most of the breakpoints occurred in
fragments 1, 2, and 3. Overall, laboratory and clinical features of CML did
not correlate with specific breakpoint fragments, but chronic-phase
duration was longer in patients with a breakpoint in fragment 2 of the bcr.
Large 3' bcr deletions were found in nine patients but did not influence
clinical outcome. DNA from one of six patients analyzed both during chronic
phase and blastic crisis showed an additional aberrant fragment, which
suggested that a second abnormal clone developed in blastic crisis.
Volume 72,
Issue 2,
pp. 485-490,
08/01/1988
Copyright © 1988 by The American Society of Hematology

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